CN111518291A - Preparation method of chitosan microsphere material - Google Patents

Preparation method of chitosan microsphere material Download PDF

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CN111518291A
CN111518291A CN201910104906.0A CN201910104906A CN111518291A CN 111518291 A CN111518291 A CN 111518291A CN 201910104906 A CN201910104906 A CN 201910104906A CN 111518291 A CN111518291 A CN 111518291A
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chitosan
microspheres
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aqueous solution
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CN111518291B (en
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蔡杰
钟奕
张俐娜
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Wuhan University WHU
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    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/12—Powdering or granulating
    • C08J3/16—Powdering or granulating by coagulating dispersions
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
    • C08J2305/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

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Abstract

The invention discloses a preparation method of a chitosan microsphere material. Firstly, adding chitosan into a bicarbonate aqueous solution, and directly stirring to dissolve the chitosan; or dissolving chitosan with dilute acid, neutralizing with alkali, adding bicarbonate, and stirring to dissolve chitosan; adding chitosan into an aqueous solution of alkali liquor or carbonate, and introducing carbon dioxide to generate bicarbonate to dissolve the chitosan; performing deacetylation reaction on chitin to generate chitosan, adjusting the concentration of alkali liquor, and introducing carbon dioxide to generate bicarbonate to dissolve the chitosan. The addition of a stabilizer helps to enhance the dissolving capacity. Taking the chitosan solution as a water phase, obtaining chitosan emulsion droplets by using a membrane emulsifier, a microfluidic device and a conventional stirring device with the assistance of an oil phase, and solidifying the emulsion droplets to obtain the chitosan gel microspheres. The invention avoids the degradation of chitosan under acidic or strong alkaline conditions, and is beneficial to ensuring the stability of the chitosan solution in the processing process.

Description

Preparation method of chitosan microsphere material
Technical Field
The invention belongs to the field of natural polymers and polymer materials, and particularly relates to a preparation method of a chitosan microsphere material.
Background
The chitosan is a deacetylated product of chitin, and when the N-deacetylation degree of the chitin is more than 55%, the chitin is converted into chitosan. The reserves of chitin and chitosan in nature are second only to cellulose, a class of natural macromolecules.
The chitosan microsphere material is a microspherical multifunctional polymer material which is prepared by taking chitosan as a main raw material, forming emulsion droplets through dissolution and emulsion formation and forming chemical crosslinking or physical crosslinking. The chitosan microsphere material not only has good biocompatibility and biodegradability, but also has antibacterial property, can promote the healing of wounds, has the hemostatic effect, and has wide application in the fields of biomedicine, drug carrier materials and the like. The preparation technology of the chitosan microspheres is a research hotspot in the technical field of new materials at present.
To prepare the chitosan microsphere material, we need to select a suitable solvent, a suitable chemical cross-linking agent and a coagulant to achieve the gelation transition of the solution. The chitosan has a large amount of hydrogen bonds among molecules, high crystallinity and insolubility in water and common organic solvents, thereby limiting the application of the chitosan. In the traditional method, a low-concentration acetic acid aqueous solution or hydrochloric acid aqueous solution is used as a solvent, chitosan is dissolved, is converted into emulsion drops after being subjected to emulsion liquefaction, and is neutralized by alkali liquor to obtain microspheres; or a chemical cross-linking agent is added into the oil phase or the water phase, the chitosan generates intermolecular cross-linking reaction, and the emulsion droplets are converted into microspheres. In recent years, inspired by the low-temperature dissolution of cellulose by an alkali/urea aqueous solvent system, Chinese scientists find that chitosan can be dissolved in an alkali/urea aqueous solution by a freezing and thawing method, and a new idea is provided for preparing a chitosan microsphere material.
Currently, alkaline aqueous solvents used to dissolve chitosan include lithium hydroxide-sodium hydroxide-urea combination (patent 201110099176.3), lithium hydroxide-potassium hydroxide-urea combination (patent 201310405191.5), sodium hydroxide-urea combination (Zhang W, Xia W.Disolution and stability of lithium in a soluble hydroxide/urea solution [ J ] Journal of Applied Polymer Science,2014,131(3): 1082. sup. -), lithium hydroxide-urea combination (Li C, Han Q, Guan Y, et al. Michael reaction of chitosan with acrylic acid in an aqueous alkali solution [ J ] Polymer Bulletin,2015,72(8): 2087. sup. -. 5.). These solvent combinations require one or more freeze-thaw cycles to solubilize the chitin and chitosan. The freezing-unfreezing process consumes a large amount of energy, has high requirements on equipment and is a great problem for industrial production.
At present, no report is available for preparing chitosan microsphere materials by dissolving chitosan in weakly alkaline aqueous solutions. The chitosan is very stable in a weak alkaline aqueous solution, is not easy to degrade, has no corrosiveness and is particularly suitable for industrial production.
Disclosure of Invention
The invention aims to provide a method for preparing a chitosan microsphere material. The application is characterized in that the chitosan is dissolved by the economic aqueous solvent system, freezing-unfreezing is not needed in the dissolving process, the solution property is stable, the degradation of chitosan molecular chains is not easy to occur, and a new method is provided for preparing the chitosan microsphere material on a large scale.
The technical scheme provided by the invention is as follows:
in a first aspect, a preparation method of a chitosan microsphere material is provided, which comprises the following steps:
(1) preparing a weakly alkaline aqueous solution, wherein the weakly alkaline aqueous solution consists of bicarbonate, a stabilizer and water; wherein the final concentration of bicarbonate is: 0.2 to 1.5 mol/kg-1The final concentration of the stabilizer is 0.6-5.0 mol/kg-1Urea or 0.3-1.2 mol/kg-1Thiourea or a mixture of the two, and the balance water;
(2) preparing a chitosan weakly alkaline aqueous solution: adding chitosan into the alkalescent aqueous solution obtained in the step (1), continuously stirring for more than 30 minutes at the temperature of not more than 35 ℃, and obtaining a transparent chitosan solution after centrifugal deaeration;
(3) preparing a chitosan microsphere material: allowing the chitosan weakly alkaline aqueous solution obtained in the step (2) to pass through any one of a membrane emulsifier, a micro-fluidic device and a conventional stirring device to form emulsion droplets under the assistance of an oil phase and an oily emulsifier, and forming microspheres after the emulsion droplets are gelatinized;
the bicarbonate is a single bicarbonate aqueous solution or a mixture of multiple bicarbonates aqueous solutions.
Preferably, the weight fraction of bicarbonate in the weakly alkaline aqueous solution prepared in the step (1) is 0.3E1.2mol·kg-1The stabilizer is 1 to 4.0 mol/kg-1Urea or 0.4-1.0 mol/kg-1Thiourea and the balance water.
In a second aspect, a preparation method of a chitosan microsphere material is provided, which comprises the following steps:
(1) dissolving chitosan in a stabilizer at a concentration of 0.1-1.0 mol/kg-1Adding a proper amount of alkali to the inorganic or organic acid aqueous solution to adjust the pH of the solution to be neutral, and separating out chitosan; the stabilizer is 0.3-5.0 mol/kg of final concentration-1Urea or 0.3-1.2 mol/kg-1Thiourea or a mixture of the two; the alkali for adjusting the pH of the solution is any one of alkali hydroxide, alkali metal carbonate, alkaline earth metal carbonate, alkali metal bicarbonate, alkaline earth metal bicarbonate, ammonia water, ammonium carbonate and ammonium bicarbonate or a mixture of the alkali hydroxide, the alkali metal carbonate, the alkaline earth metal bicarbonate and the ammonia water; the inorganic or organic acid is preferably acetic acid, hydrochloric acid, citric acid, etc.;
(2) adding bicarbonate into the mixture of chitosan and water in the step (1), continuously stirring for more than 10 minutes under the condition of the freezing point to 35 ℃, dissolving chitosan, and obtaining a transparent chitosan solution after centrifugal deaeration; the final concentration of the bicarbonate is 0.2-1.5 mol/kg-1；
(3) Preparing a chitosan microsphere material: allowing the chitosan weakly alkaline aqueous solution obtained in the step (2) to pass through any one of a membrane emulsifier, a micro-fluidic device and a conventional stirring device to form emulsion droplets under the assistance of an oil phase and an oily emulsifier, and forming microspheres after the emulsion droplets are gelatinized;
the bicarbonate is a single bicarbonate aqueous solution or a mixture of multiple bicarbonates aqueous solutions.
Preferably, the final concentration range of the stabilizer added in the step (1) is 1.0-4.0 mol/kg-1Urea or 0.4-1.0 mol/kg-1Thiourea; the final concentration range of the bicarbonate in the step (2) is preferably 0.3-1.2 mol/kg-1。
In a third aspect, a preparation method of a chitosan microsphere material is provided, which comprises the following steps:
(1) preparation of alkaliAn aqueous alkaline solution consisting of an alkaline hydroxide or carbonate, a stabilizer and water; wherein the final concentration of the alkali hydroxide is 0.2 to 1.5 mol/kg-1The final concentration of carbonate is 0.10 to 0.75 mol/kg-1The final concentration of the stabilizer is 0.6-5.0 mol/kg-1Urea or 0.3-1.2 mol/kg-1Thiourea or a mixture of the thiourea and the water;
(2) adding chitosan into the alkaline aqueous solution obtained in the step (1), introducing carbon dioxide, continuously stirring for more than 30 minutes under the condition that the freezing point is 35 ℃, dissolving the chitosan when the pH value of the solution is about 7-10, and performing centrifugal deaeration to obtain a transparent chitosan solution;
(3) preparing a chitosan microsphere material: allowing the chitosan weakly alkaline aqueous solution obtained in the step (2) to pass through any one of a membrane emulsifier, a micro-fluidic device and a conventional stirring device to form emulsion droplets under the assistance of an oil phase and an oily emulsifier, and forming microspheres after the emulsion droplets are gelatinized;
the alkaline hydroxide is metal hydroxide, ammonium hydroxide, quaternary ammonium base, preferably lithium hydroxide, sodium hydroxide, potassium hydroxide, ammonium hydroxide or a mixture thereof; the carbonate is lithium carbonate, sodium carbonate, potassium carbonate, ammonium carbonate or a mixture thereof.
Preferably, the final concentration of the hydroxide in the alkaline aqueous solution prepared in the step (1) is preferably 0.3-1.2 mol/kg-1The final concentration of carbonate is preferably 0.15 to 0.6 mol/kg-1The final concentration range of the stabilizer is preferably 1.0-4.0 mol/kg-1Urea or 0.4-1.0 mol/kg-1Thiourea and the balance water.
In a fourth aspect, a preparation method of a chitosan microsphere material is provided, which comprises the following steps:
(1) chitin and the mass molar concentration of 8.0-12.5 mol/kg-1Mixing sodium hydroxide aqueous solution or potassium hydroxide aqueous solution, heating to perform deacetylation reaction to generate chitosan;
(2) adjusting the final concentration of sodium hydroxide or potassium hydroxide in the mixture obtained in step (1)0.2 to 1.5 mol/kg-1Reducing the temperature of the mixture to between the freezing point and 35 ℃, adding a stabilizer, introducing carbon dioxide at room temperature, and when the pH value of the solution is about 7-10, converting sodium hydroxide or potassium hydroxide into bicarbonate and dissolving chitosan; the stabilizer is 0.6-5.0 mol/kg of final concentration-1Urea or 0.4-1.0 mol/kg-1One or a mixture of two of thiourea; preferably, the final concentration of the stabilizer is 1.0-4.0 mol/kg-1Urea or 0.4-1.0 mol/kg-1One or a mixture of two of thiourea; preferably, the final concentration of the bicarbonate is 0.3-1.2 mol-kg-1；
(3) Preparing a chitosan microsphere material: allowing the chitosan weakly alkaline aqueous solution obtained in the step (2) to pass through any one of a membrane emulsifier, a micro-fluidic device and a conventional stirring device to form emulsion droplets under the assistance of an oil phase and an oily emulsifier, and forming microspheres after the emulsion droplets are gelatinized;
the bicarbonate is a single bicarbonate aqueous solution or a mixture of multiple bicarbonates aqueous solutions.
Preferably, the method for adjusting the concentration of sodium hydroxide or potassium hydroxide in the mixture in step (2) is: filtering and squeezing the mixture obtained in the step (1) to remove excessive sodium hydroxide or potassium hydroxide aqueous solution, and adding a proper amount of water to ensure that the final concentration of the sodium hydroxide or the potassium hydroxide in the mixture is 0.2-1.5 mol/kg-1。
Preferably, the bicarbonate includes alkali metal bicarbonate, alkaline earth metal bicarbonate, ammonium bicarbonate, preferably one or more of sodium bicarbonate, potassium bicarbonate, ammonium bicarbonate, magnesium bicarbonate.
Preferably, the oil phase in step (3) of the preparation method is composed of an oily substance which is liquid at normal temperature and is immiscible with water and an oil-soluble emulsifier, and the oily substance can be liquid paraffin, petroleum ether, olive oil, cottonseed oil, soybean oil, sunflower seed oil, other alkanes hydrocarbons and the like; as the oily emulsifier, it is necessary to use an oily substance which is dissolved in the oil used, and sorbitan sesquioleate (Arlace183), polymers of glyceryl ether (e.g., PO-500, PO-310), polyoxyethylene hydrogenated castor oil, sorbitan trioleate (span 85), sorbitan monooleate (span 80), sorbitan tristearate (span 65), Tween 80, lipophilic-hydrophilic block copolymer and the like can be used. The concentration of the emulsifier in the oil phase is 0.5-10%.
Preferably, the volume ratio of the chitosan aqueous solution to the oil phase in the step (3) in the preparation method is 1: 1-1: 1000, and preferably 1: 2-1: 100.
Preferably, the emulsion droplets are obtained by using a membrane emulsifier by pressing an aqueous chitosan solution (aqueous phase) into the oil phase through a microporous membrane with pressure to obtain emulsion droplets with uniform size; the method for obtaining the emulsion drop by utilizing the microfluidic device is that a micro pump is used for conveying an oil phase and a water phase to two intersected channels in a microfluidic chip, and the oil phase is used as a continuous phase to separate the water phase to form a monodisperse emulsion drop; the method for obtaining the emulsion droplets by using the conventional stirring device is to mix the oil phase and the water phase, perform mechanical stirring, and disperse the water phase into the oil phase to form the emulsion droplets.
The solidification mode of converting emulsion droplets into microspheres in the preparation method adopts a physical method or a chemical method. Comprises a chemical cross-linking agent which can cause the chitosan molecule to generate chemical cross-linking reaction and a coagulating agent which can cause the chitosan to be dehydrated.
The chemical cross-linking agent is a common cross-linking agent which is equivalent to the chitosan monomer with the molar ratio of 0.1-10, and comprises aldehyde cross-linking agents, glycidyl ether cross-linking agents, epoxy compounds, iridoids and polyphenols, preferably glutaraldehyde, epoxy chloropropane, genipin and procyanidine;
the coagulant is a mixed aqueous solution of any one or more of amide, dimethyl sulfoxide, ethyl acetate, acetone, alcohols, salts and acids; the preferable salt concentration is 0-40 wt%, the acid concentration is 0-20 wt%, and the alcohol concentration is 0-100 wt%; the alcohol is preferably methanol or ethanol; the salt is preferably ammonium salt, sodium salt, potassium salt, magnesium salt, calcium salt, and aluminum salt;
after the curing reaction is finished, washing the obtained microspheres with petroleum ether, acetone, ethanol, acetone and water in sequence, and drying to obtain the chitosan microsphere finished product.
In a fifth aspect, a chitosan microsphere material is provided, which is prepared by any one of the above methods for preparing a chitosan microsphere material.
In a sixth aspect, a method for preparing multifunctional chitosan microspheres is provided, wherein functional organic or inorganic additives can be introduced in the process of preparing the chitosan microspheres, or different macromolecules can be introduced for blending.
Preferably, the functional organic or inorganic additive comprises one or more of a plasticizer, a reinforcing agent, a refractory additive, a dye, an optical stabilizer, an antibacterial bacteriostatic agent, a conductive material and a surfactant.
Preferably, the functional organic or inorganic additive includes graphene and its derivatives, carbon nanotubes and their derivatives, metal or metal oxide nanoparticles, organic framework compounds or molybdenum disulfide, and the like, and the blended polymer includes polymer nanofibers, animal proteins, vegetable proteins, alginates, collagen, cellulose and its derivatives, conductive polymers, polyvinyl alcohol, polyethylene glycol, and the like.
In a seventh aspect, a multifunctional chitosan microsphere material is provided, which is prepared by the method for preparing the multifunctional chitosan microsphere of the sixth aspect.
And in an eighth aspect, a preparation method of nitrogen-doped carbon aerogel microspheres is provided, wherein the chitosan microspheres or multifunctional chitosan microspheres are subjected to heat treatment at a temperature of more than 150 ℃ under the protection of inert gas atmosphere to obtain the carbon aerogel microspheres.
Compared with the prior art, the invention provides a green and energy-saving method for obtaining the high-quality chitosan microsphere material. The method has the advantages that the adopted bicarbonate aqueous solution is a weakly alkaline solvent system, has no corrosivity, has good solution stability, has mild conditions in the process of preparing the chitosan microspheres from the chitosan solution, does not need freezing-unfreezing, and has green and environment-friendly preparation method and no toxic and harmful substance residues.
Detailed Description
Further features and advantages of the present invention will be understood from the following detailed description. The examples provided are merely illustrative of the method of the present invention and do not limit the remainder of the disclosure in any way.
The chitosan used in the following examples and comparative examples is extracted from natural shrimp shell, crab shell, squid parietal bone, diatom, insect and other organisms containing alpha-chitin and beta-chitin, and the specific extraction steps are immersing with alkali liquor to remove protein, immersing with acid liquor to remove inorganic salt, decoloring with oxidant, washing with water and drying to obtain purified chitin. The chitosan is prepared by deacetylation reaction of chitin in sodium hydroxide or potassium hydroxide aqueous solution, or is a pure chitosan product purchased from a reagent company.
Example 1
Soaking shrimp shell in alkali solution to remove protein, soaking in acid solution to remove inorganic salt, and decolorizing with hydrogen peroxide water solution to obtain purified chitin. Chitin is added at a concentration of 12.5 mol/kg-1Heating the mixture in sodium hydroxide aqueous solution for 1h to perform deacetylation reaction, and obtaining chitosan with deacetylation degree of about 70%. The concentration of 0.2 mol/kg is prepared in advance-10.6 mol/kg of lithium bicarbonate-197g of urea aqueous solution, 3g of chitosan is added, the mixture is stirred for 3 hours at the temperature of 10 ℃, and a transparent chitosan solution is obtained after centrifugal deaeration. . Mixing chitosan stock solution and 2 times volume ratio of oil phase (the liquid paraffin contains 0.5 percent of span 80), mixing chitosan monomer and epoxy chloropropane with the molar ratio of 1:10, and stirring at the rotating speed of 800rpm for 1h to form the microsphere. And pouring the obtained microspheres into an ethanol water solution with the water content of 90 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the morphology of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 20 microns. The BET specific surface area is 360m by nitrogen adsorption2/g。
Example 2
Soaking crab shell with alkali solution to remove protein, soaking with acid solution to remove inorganic salt, and decolorizing with hydrogen peroxide solution to obtain purified chitin. Adding chitin to the concentration of 8.0mol·kg-1Heating the mixture in a potassium hydroxide aqueous solution for 2 hours to perform deacetylation reaction to obtain chitosan with the deacetylation degree of about 60%. The concentration of 0.2 mol/kg is prepared in advance-1Sodium bicarbonate-0.6 mol/kg-197g of urea aqueous solution, 3g of chitosan is added, the mixture is stirred for 60min at the temperature of 20 ℃, and the transparent chitosan solution is obtained after centrifugal deaeration. The hydrophobic membrane with the pore diameter of 4.7 microns is soaked in the lipophilic substance, so that the porous membrane is sufficiently wetted to ensure that the hydrophobic membrane on the membrane is completely spread. Adding span 85 into 1L of mixed oil phase of liquid paraffin and petroleum ether, and stirring until completely dissolving to obtain oil phase (the volume ratio of liquid paraffin to petroleum ether is 1:1, and the oil phase contains 1% span 85). 100g of chitosan solution is pressed into an oil phase through a hydrophobic microporous membrane with uniform aperture under certain pressure to obtain chitosan emulsion. Adding chitosan monomer and glutaraldehyde with the molar ratio of 1:1 to the emulsion, mixing, and stirring at the rotating speed of 300rpm for 2h to form microspheres. Washing the obtained microspheres with petroleum ether, acetone, ethanol and acetone in sequence, washing with water, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 15 microns. The BET specific surface area is 320m by nitrogen adsorption2/g。
Example 3
Soaking squid bones in alkali liquor to remove proteins, and soaking in acid liquor to remove inorganic salts to obtain purified chitin. Chitin is added at a concentration of 10.0 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 2 hours to perform deacetylation reaction to obtain chitosan with the deacetylation degree of about 60%. The concentration of 0.2 mol/kg is prepared in advance-1Potassium bicarbonate-0.6 mol/kg-197g of urea aqueous solution, 3g of chitosan is added, the mixture is stirred for 180min at the temperature of 30 ℃, and the transparent chitosan solution is obtained after centrifugal deaeration. The hydrophobic membrane with the aperture of 13 microns is soaked in the lipophilic substance, so that the porous membrane is sufficiently wetted to ensure that the hydrophobic link on the membrane is completely spread. Adding an oil-soluble emulsifier into a mixed oil phase of 1L of liquid paraffin and petroleum ether, and stirring until the oil-soluble emulsifier is completely dissolved to form an oil phase (the volume ratio of the liquid paraffin to the petroleum ether is 1:1, and the oil phase contains 1% of span 85). 100g of chitosan solution is added intoAnd (3) pressing the mixture into an oil phase through a hydrophobic microporous membrane with uniform pore diameter under constant pressure to obtain the chitosan emulsion. Adding chitosan monomer and genipin with the molar ratio of 1:10 into the emulsion, mixing, and stirring at 300rpm for 2h to form microspheres. And pouring the obtained microspheres into an ethanol water solution with the water content of 80 wt% for regeneration, centrifuging, washing precipitates with petroleum ether, acetone, ethanol acetone and water respectively, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 400m by nitrogen adsorption2/g。
Example 4
Soaking shrimp shell in alkali solution to remove protein, soaking in acid solution to remove inorganic salt, and decolorizing with hydrogen peroxide water solution to obtain purified chitin. Chitin is added at a concentration of 10.0 mol/kg-1Heating the mixture in sodium hydroxide aqueous solution for 2 hours to carry out deacetylation reaction, and obtaining the chitosan with deacetylation degree of about 70%. The concentration of 0.4 mol/kg is prepared in advance-1Ammonium bicarbonate-0.6 mol/kg-197g of urea aqueous solution, 3g of chitosan is added, the mixture is stirred for 60min at the temperature of 0 ℃, and the transparent chitosan solution is obtained after centrifugal deaeration. The hydrophobic membrane with the aperture of 19 microns is soaked in the lipophilic substance, so that the porous membrane is sufficiently wetted to ensure that the hydrophobic link on the membrane is completely spread. Adding span 80 into 1L of mixed oil phase of liquid paraffin and petroleum ether, and stirring until the mixture is completely dissolved to obtain oil phase (the volume ratio of the liquid paraffin to the petroleum ether is 1:1, and the oil phase contains 5% of span 80). 100g of chitosan solution is pressed into an oil phase through a hydrophobic microporous membrane with uniform aperture under certain pressure to obtain chitosan emulsion. Adding chitosan monomer and genipin with the molar ratio of 1:0.1 into the emulsion, mixing, and stirring at 300rpm for 2h to form microspheres. And pouring the obtained microspheres into an ethanol water solution with the water content of 90 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres to obtain the average size of 60 microns. The BET specific surface area is 360m by nitrogen adsorption2/g。
Example 5
Soaking crab shell with alkali solution to remove protein, soaking with acid solution to remove inorganic salt, and decolorizing with hydrogen peroxide water solution to obtain purified chitin. Chitin with concentration of 8.0 mol/kg-1Heating the mixture in sodium hydroxide aqueous solution for 2h to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 60%. The concentration of 0.4 mol/kg is prepared in advance-1Magnesium bicarbonate-0.6 mol/kg-197g of urea aqueous solution, 3g of chitosan is added, the mixture is stirred for 60min at the temperature of 0 ℃, and the transparent chitosan solution is obtained after centrifugal deaeration. Adding span 80 into 1L of mixed oil phase of liquid paraffin and petroleum ether, and stirring until the mixture is completely dissolved to obtain oil phase (the volume ratio of the liquid paraffin to the petroleum ether is 1:1, and the oil phase contains 10% of span 80). Conveying the chitosan solution and the oil phase to a micro-fluidic chip (the diameter of an oil-phase channel in the chip is 350 microns, and the diameter of a water-phase channel in the chip is 16 microns) through a micro-pump to form monodisperse droplets; placing the collected liquid drops into a magnesium chloride solution with the salt content of 40 wt% for gelation, and removing the organic solvent; and pouring the obtained microspheres into an ethanol water solution with the water content of 70 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the morphology of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 40 micrometers. The BET specific surface area is 390m by nitrogen adsorption2/g。
Example 6
Soaking the top bone of the squid in alkali liquor to remove protein, and soaking in acid liquor to remove inorganic salt to obtain purified chitin. Chitin with concentration of 9.0 mol/kg-1Heating the mixture in sodium hydroxide aqueous solution for 2 hours to carry out deacetylation reaction, and obtaining the chitosan with deacetylation degree of about 70%. The concentration of 0.3 mol/kg is prepared in advance-15 mol/kg of lithium bicarbonate-195g of urea aqueous solution, 5g of chitosan is added, the mixture is stirred for 60min at the temperature of 0 ℃, and the transparent chitosan solution is obtained after centrifugal deaeration. Adding span 85 into 1L mixed oil phase of liquid paraffin and petroleum ether, stirring to completely dissolve as oil phase (volume of liquid paraffin and petroleum ether)The ratio is 1:1, the oil phase contains 1 percent of span 85). Conveying the chitosan solution and the oil phase to a micro-fluidic chip (the diameter of an oil-phase channel in the chip is 350 microns, and the diameter of a water-phase channel in the chip is 50 microns) through a micro-pump to form monodisperse droplets; placing the collected liquid drops into a magnesium chloride solution with the salt content of 20 wt% for gelation, and removing the organic solvent; and pouring the obtained microspheres into an ethanol water solution with the water content of 50 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the morphology of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres to obtain the average size of 75 microns. The BET specific surface area is 430m by nitrogen adsorption2/g。
Example 7
Soaking shrimp shell in alkali solution to remove protein, and soaking in acid solution to remove inorganic salt to obtain purified chitin. Adding chitin to the solution at a concentration of 11.5 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 0.3 mol/kg is prepared in advance-15 mol/kg sodium bicarbonate-195g of urea aqueous solution, 5g of chitosan is added, the mixture is stirred for 60min at 10 ℃, and the transparent chitosan solution is obtained after centrifugal deaeration. Adding span 80 into 1L of mixed oil phase of liquid paraffin and petroleum ether, and stirring until the mixture is completely dissolved to obtain oil phase (the volume ratio of the liquid paraffin to the petroleum ether is 1:1, and the oil phase contains 1% of span 80). Conveying the chitosan solution and the oil phase to a micro-fluidic chip (the diameter of an oil-phase channel in the chip is 350 microns, and the diameter of a water-phase channel in the chip is 30 microns) through a micro-pump to form monodisperse droplets; placing the collected liquid drops into a magnesium chloride solution with the salt content of 20 wt% for gelation, and removing the organic solvent; and pouring the obtained microspheres into an ethanol water solution with the water content of 30 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the morphology of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 42 microns. The BET specific surface area is 380m measured by nitrogen adsorption2/g。
Example 8
Soaking crab shell with alkali solution to remove protein, and soaking with acid solution to remove inorganic salt to obtain purified chitin. Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 0.3 mol/kg is prepared in advance-15 mol/kg of potassium bicarbonate-195g of urea aqueous solution, 5g of chitosan is added, the mixture is stirred for 120min at the temperature of 20 ℃, and the transparent chitosan solution is obtained after centrifugal deaeration. Mixing chitosan stock solution and 5 times volume ratio of oil phase (olive oil and Tween 80, wherein the concentration of Tween 80 is 0.5%) which is equivalent to procyanidin with 1 time molar ratio of chitosan monomer, and stirring at 1000rpm for 2h to form microspheres. And pouring the obtained microspheres into an ethanol water solution with the water content of 10 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the morphology of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 20 microns. The BET specific surface area is 360m by nitrogen adsorption2/g。
Example 9
Soaking shrimp shell in alkali solution to remove protein, and soaking in acid solution to remove inorganic salt to obtain purified chitin. Chitin is added at a concentration of 12.5 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with a deacetylation degree of about 80%. The concentration of 0.3 mol/kg is prepared in advance-15 mol/kg ammonium bicarbonate-195g of urea aqueous solution, 5g of chitosan is added, the mixture is stirred for 120min at 10 ℃, and the transparent chitosan solution is obtained after centrifugal deaeration. The chitosan stock solution is mixed with an oil phase (olive oil and Tween 80, wherein the Tween 80 accounts for 6%) with the volume ratio of 5 times, and glutaraldehyde with the molar ratio of 0.1 time that of the chitosan monomer is mixed, and then the mixture is stirred at the rotating speed of 1000rpm for 2 hours to form microspheres. And (3) pouring the obtained microspheres into ethanol for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. Observing the morphology of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres to obtain the chitosan microspheres with the average size of 30 microns. The BET specific surface area is 290m by nitrogen adsorption2/g。
Example 10
Soaking shrimp shell in alkali solution to remove protein, and soaking in acid solution to remove inorganic salt to obtain purified chitin. Chitin with mass fraction of 11.0 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 0.3 mol/kg is prepared in advance-1Magnesium bicarbonate-5 mol/kg-195g of urea aqueous solution, 5g of chitosan is added, the mixture is stirred for 120min at 10 ℃, and the transparent chitosan solution is obtained after centrifugal deaeration. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (liquid paraffin and span 80, span 80 accounts for 1%) which is equivalent to 10 times mole ratio of glutaraldehyde of chitosan monomer, mixing, and stirring at 1000rpm for 2h to form microspheres. And pouring the obtained microspheres into a methanol water solution with the water content of 70 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 15 microns. The BET specific surface area is 420m by nitrogen adsorption2/g。
Example 11
Chitin is added at a concentration of 10.0 mol/kg-1Heating the mixture in sodium hydroxide aqueous solution for 2 hours to carry out deacetylation reaction, and obtaining the chitosan with deacetylation degree of about 70%. The concentration of 0.8 mol/kg is prepared in advance-11 mol/kg of lithium bicarbonate-1Adding 94g of urea aqueous solution into 6g of chitosan, stirring for 30min at 0 ℃, and obtaining a transparent chitosan solution after centrifugal deaeration. Mixing chitosan stock solution and 5 times volume ratio of oil phase (liquid paraffin and span 80, span 80 accounts for 0.5%) which is equivalent to 2 times mole ratio of glutaraldehyde of chitosan monomer, and stirring at 1000rpm for 2h to form microspheres. And pouring the obtained microspheres into a methanol water solution with the water content of 50 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. Observing the morphology of the chitosan microspheres by using a scanning electron microscope, and counting the straightness of the microspheresDiameter, with an average size of 10 microns. The BET specific surface area is 430m by nitrogen adsorption2/g。
Example 12
Chitin is added at a concentration of 10.0 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 0.8 mol/kg is prepared in advance-1Sodium bicarbonate-1 mol/kg-1Adding 94g of urea aqueous solution into 6g of chitosan, stirring for 100min at 10 ℃, and obtaining a transparent chitosan solution after centrifugal deaeration. Mixing the chitosan stock solution and an oil phase (olive oil and span 80, the concentration of span 80 is 0.5%) with the volume ratio of 5 times, and stirring at the rotating speed of 1000rpm for 2 hours to form microspheres. And pouring the obtained microspheres into a methanol water solution with the water content of 30 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 2 microns. The BET specific surface area is 470m by nitrogen adsorption2/g。
Example 13
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 0.8 mol/kg is prepared in advance-1Potassium bicarbonate-1 mol/kg-1Adding 94g of urea aqueous solution into 6g of chitosan, stirring for 180min at 20 ℃, and obtaining a transparent chitosan solution after centrifugal deaeration. Mixing the chitosan stock solution and an oil phase (olive oil and span 80, the concentration of span 80 is 0.5%) with the volume ratio of 5 times, and stirring at the rotating speed of 1000rpm for 2 hours to form microspheres. And pouring the obtained microspheres into a methanol water solution with the water content of 10 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres to obtain the average size of 5 microns. The BET specific surface area is 460m measured by nitrogen adsorption2/g。
Example 14
Will firstThe concentration of chitin is 11.0 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 0.8 mol/kg is prepared in advance-1Ammonium bicarbonate-1 mol/kg-1Adding 94g of urea aqueous solution into 6g of chitosan, stirring for 100min at 10 ℃, and obtaining a transparent chitosan solution after centrifugal deaeration. Mixing the chitosan stock solution with 10 times volume ratio of oil phase (olive oil and Tween 80, Tween 80 accounts for 1%), and stirring at 1000rpm for 2h to form microspheres. And (3) pouring the obtained microspheres into methanol for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the morphology of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 40 micrometers. The BET specific surface area is 350m by nitrogen adsorption2/g。
Example 15
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 0.8 mol/kg is prepared in advance-1Magnesium bicarbonate-1 mol/kg-1Adding 94g of urea aqueous solution into 6g of chitosan, stirring for 100min at 10 ℃, and obtaining a transparent chitosan solution after centrifugal deaeration. Mixing the chitosan stock solution and an oil phase (olive oil and Tween 80, wherein the concentration of the Tween 80 is 0.5%) with the volume ratio of 5 times, and stirring at the rotating speed of 1000rpm for 2h to form the microspheres. And pouring the obtained microspheres into a magnesium chloride aqueous solution with the mass fraction of 40 wt% for regeneration, centrifuging, taking precipitates, washing the precipitates with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the morphology of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 20 microns. The BET specific surface area is 340m by nitrogen adsorption2/g。
Example 16
Chitin is added at a concentration of 10.0 mol/kg-1Heating the mixture in sodium hydroxide aqueous solution for 2 hours to carry out deacetylation reaction, and obtaining the chitosan with deacetylation degree of about 70%. The concentration of 1.2 mol/kg was prepared in advance-1Lithium bicarbonate-4 mol·kg-197g of urea aqueous solution, 3g of chitosan is added, the mixture is stirred for 60min at the temperature of 0 ℃, and the transparent chitosan solution is obtained after centrifugal deaeration. Mixing the chitosan stock solution with 5 times volume ratio of oil phase (olive oil and Tween 80, Tween 80 accounts for 1%), stirring at 1000rpm for 2h to form microspheres. And pouring the obtained microspheres into a potassium chloride aqueous solution with the mass fraction of 20 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 290m by nitrogen adsorption2/g。
Example 17
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 1.2 mol/kg was prepared in advance-1Sodium bicarbonate-4 mol/kg-1Adding 3g of chitosan into 97g of urea aqueous solution, stirring for 120min at 10 ℃, and performing centrifugal deaeration to obtain a transparent chitosan solution. Mixing the chitosan stock solution and an oil phase (olive oil and span 80, the concentration of span 80 is 0.5%) with the volume ratio of 5 times, and stirring at the rotating speed of 1000rpm for 2 hours to form microspheres. And pouring the obtained microspheres into a sodium sulfate aqueous solution with the mass fraction of 10 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 320m by nitrogen adsorption2/g。
Example 18
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 1.2 mol/kg was prepared in advance-1Potassium bicarbonate-4 mol/kg-1Adding 3g of chitosan into 97g of urea aqueous solution, stirring for 120min at 20 ℃, and performing centrifugal deaeration to obtain a transparent chitosan solution. Chitosan stock solution and 2.5 times volume ratio of oil phase (fructus Canarii albi)Oil and Tween 80, wherein the concentration of Tween 80 is 0.5%), and the microspheres are formed after stirring at the rotating speed of 900rpm for 2h at room temperature. And pouring the obtained microspheres into a calcium chloride aqueous solution with the mass fraction of 5 wt% for regeneration, centrifuging, taking precipitates, washing the precipitates with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the morphology of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 40 micrometers. The BET specific surface area is 350m by nitrogen adsorption2/g。
Example 19
Adding chitin to the solution at a concentration of 11.5 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 1.2 mol/kg was prepared in advance-1Ammonium bicarbonate-4 mol/kg-197g of urea aqueous solution, 3g of chitosan is added, the mixture is stirred for 60min at the temperature of 10 ℃, and the transparent chitosan solution is obtained after centrifugal deaeration. Mixing chitosan stock solution with 5 times volume ratio of oil phase (olive oil and span 80, span 80 accounts for 5%), 1 time molar ratio of chitosan monomer of epichlorohydrin, stirring at room temperature at 900rpm for 2h to form microspheres. And pouring the obtained microspheres into an acetic acid aqueous solution with the mass fraction of 20 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres to obtain the average size of 60 microns. The BET specific surface area is 260m by nitrogen adsorption2/g。
Example 20
Chitin is added at a concentration of 12.5 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 1.2 mol/kg was prepared in advance-1Magnesium bicarbonate-4 mol/kg-197g of urea aqueous solution, 3g of chitosan is added, the mixture is stirred for 60min at the temperature of 10 ℃, and the transparent chitosan solution is obtained after centrifugal deaeration. Mixing the chitosan stock solution and an oil phase (olive oil and Tween 80, wherein the concentration of the Tween 80 is 0.5%) in a volume ratio of 5 times, and stirring at the rotating speed of 900rpm for 2h at room temperature to form microspheres.And pouring the obtained microspheres into a sulfuric acid aqueous solution with the mass fraction of 10 wt% for regeneration, centrifuging, taking precipitates, washing the precipitates with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the morphology of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 70 microns. The BET specific surface area is 360m by nitrogen adsorption2/g。
Example 21
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating the mixture in sodium hydroxide aqueous solution for 2 hours to carry out deacetylation reaction, and obtaining the chitosan with deacetylation degree of about 70%. The concentration of 1.5 mol/kg was prepared in advance-12 mol/kg of lithium bicarbonate-1Adding 98g of urea aqueous solution, adding 2g of chitosan, stirring for 60min at 0 ℃, dissolving the chitosan, and performing centrifugal deaeration to obtain a transparent chitosan solution. Mixing the chitosan stock solution with 100 times volume ratio of oil phase (isooctane and span 80, span 80 is 0.5 percent), stirring at the room temperature at the rotating speed of 900rpm for 2 hours to form microspheres. And pouring the obtained microspheres into a phosphoric acid aqueous solution with the mass fraction of 5 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 250m by nitrogen adsorption2/g。
Example 22
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 90min to perform deacetylation reaction to obtain chitosan with a deacetylation degree of about 80%. The concentration of 1.5 mol/kg was prepared in advance-12 mol/kg sodium bicarbonate-1Adding 98g of urea aqueous solution into 2g of chitosan, stirring for 30min at 10 ℃, and obtaining a transparent chitosan solution after centrifugal deaeration. Mixing chitosan stock solution with 100 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%), stirring at room temperature at 900rpm for 2 hr to form microsphere. Pouring the obtained microspheres into 10 wt% potassium chloride-20 wt% ethanol water solution for regeneration, centrifuging, and sequentially using petroleum ether, acetone and ethylWashing with alcohol, acetone and water, and freeze-drying to obtain the chitosan microsphere. And observing the morphology of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 120 microns. The BET specific surface area is 280m by nitrogen adsorption2/g。
Example 23
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating in potassium hydroxide water solution for 50min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 1.5 mol/kg was prepared in advance-12 mol/kg of potassium bicarbonate-1Adding 98g of urea aqueous solution into 2g of chitosan, stirring for 200min at 15 ℃, and obtaining a transparent chitosan solution after centrifugal deaeration. Mixing chitosan stock solution and 50 times volume ratio of oil phase (olive oil and span 80, span 80 concentration is 0.5%), stirring at room temperature at 900rpm for 2h to form microspheres. And pouring the obtained microspheres into an aqueous solution of 10 wt% acetic acid-60 wt% ethanol for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres to obtain the average size of 150 microns. The BET specific surface area is 290m by nitrogen adsorption2/g。
Example 24
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating in potassium hydroxide water solution for 50min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 1.5 mol/kg was prepared in advance-12 mol/kg ammonium bicarbonate-1Adding 98g of urea aqueous solution into 2g of chitosan, stirring for 120min at 5 ℃, and obtaining a transparent chitosan solution after centrifugal deaeration. Mixing the chitosan stock solution and 50 times volume ratio of oil phase (olive oil and Tween 80, the concentration of Tween 80 is 0.5%), stirring at room temperature at 900rpm for 2h to form microspheres. And pouring the obtained microspheres into a magnesium chloride-60 wt% ethanol aqueous solution with the mass fraction of 20 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. Observing the shape of the chitosan microsphere by using a scanning electron microscopeBy way of example, the average size of the microspheres is 100 microns by statistical diameter. The BET specific surface area is 360m by nitrogen adsorption2/g。
Example 25
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating in potassium hydroxide water solution for 50min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 1.5 mol/kg was prepared in advance-12 mol/kg of magnesium bicarbonate-1Adding 98g of urea aqueous solution into 2g of chitosan, stirring for 120min at 5 ℃, and obtaining a transparent chitosan solution after centrifugal deaeration. Mixing the chitosan stock solution and 10 times volume ratio of oil phase (olive oil and Tween 80, the concentration of Tween 80 is 0.5%), stirring at room temperature at the rotation speed of 900rpm for 2h to form microspheres. And pouring the obtained microspheres into an aqueous solution of aluminum chloride with the mass fraction of 20 wt% -60 wt% ethanol for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the morphology of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 20 microns. The BET specific surface area is 360m by nitrogen adsorption2/g。
Example 26
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating in potassium hydroxide water solution for 50min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 0.3 mol/kg is prepared in advance-10.3 mol/kg of lithium bicarbonate-1Sodium bicarbonate-0.3 mol/kg-1Potassium bicarbonate-0.3 mol/kg-1Ammonium bicarbonate-0.3 mol/kg-12 mol/kg of magnesium bicarbonate-1Adding 98g of urea aqueous solution into 2g of chitosan, stirring for 120min at 5 ℃, and obtaining a transparent chitosan solution after centrifugal deaeration. Mixing the chitosan stock solution and 10 times volume ratio of oil phase (olive oil and Tween 80, the concentration of Tween 80 is 0.5%), stirring at room temperature at the rotation speed of 900rpm for 2h to form microspheres. And pouring the obtained microspheres into an ethanol water solution with the water content of 70 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. By scanning electron microscopeThe morphology of the chitosan microspheres was observed, and the average size was 40 μm by counting the diameter of the microspheres. The BET specific surface area is 310m by nitrogen adsorption2/g。
Example 27
Chitin is added to the mixture with the concentration of 11.0 mol/kg-1Heating the mixture in sodium hydroxide aqueous solution for 1h to perform deacetylation reaction, and obtaining chitosan with deacetylation degree of about 70%. The concentration of 0.2 mol/kg is prepared in advance-10.3 mol/kg of lithium bicarbonate-197g of thiourea aqueous solution, 3g of chitosan is added, the mixture is stirred for 3 hours at the temperature of 10 ℃, and a transparent chitosan solution is obtained after centrifugal deaeration. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (liquid paraffin and span 80, span 80 is 0.5 percent), stirring at room temperature and 900rpm for 2h to form microspheres. And pouring the obtained microspheres into an ethanol water solution with the water content of 50 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres to obtain the average size of 60 microns. The BET specific surface area is 270m by nitrogen adsorption2/g。
Example 28
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 1 hour for deacetylation reaction to obtain chitosan with a deacetylation degree of about 80%. The concentration of 0.2 mol/kg is prepared in advance-1Sodium bicarbonate-0.3 mol/kg-1And adding 97g of thiourea aqueous solution into 3g of chitosan, stirring for 60min at 20 ℃, and centrifuging and defoaming to obtain a transparent chitosan solution. Mixing chitosan stock solution with 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%), stirring at room temperature at 900rpm for 2 hr to form microsphere. And pouring the obtained microspheres into an ethanol water solution with the water content of 30 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 320m by nitrogen adsorption2/g。
Example 29
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 2 hours to perform deacetylation reaction to obtain chitosan with the deacetylation degree of about 60%. The concentration of 0.2 mol/kg is prepared in advance-1Potassium bicarbonate-0.3 mol/kg-1And adding 97g of thiourea aqueous solution into 3g of chitosan, stirring for 180min at 30 ℃, and centrifuging and defoaming to obtain a transparent chitosan solution. Mixing the chitosan stock solution with 5 times volume ratio of oil phase (isooctane and span 80, span 80 is 0.5 percent), stirring at room temperature at 900rpm for 2h to form microspheres. And pouring the obtained microspheres into an ethanol water solution with the water content of 10 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres to obtain the average size of 100 microns. The BET specific surface area is 230m by nitrogen adsorption2/g。
Example 30
Chitin is added at a concentration of 10.0 mol/kg-1Heating the mixture in sodium hydroxide aqueous solution for 2 hours to carry out deacetylation reaction, and obtaining the chitosan with deacetylation degree of about 70%. The concentration of 0.4 mol/kg is prepared in advance-1Ammonium bicarbonate-0.3 mol/kg-1And adding 97g of thiourea aqueous solution into 3g of chitosan, stirring for 60min at 0 ℃, and centrifuging and defoaming to obtain a transparent chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. And (3) pouring the obtained microspheres into ethanol for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 250m by nitrogen adsorption2/g。
Example 31
Chitin is added at a concentration of 12.5 mol/kg-1Heating in sodium hydroxide water solution for 2h for deacetylation reaction to obtainTo chitosan with deacetylation degree of about 70%. The concentration of 0.4 mol/kg is prepared in advance-1Magnesium bicarbonate-0.3 mol/kg-1And adding 97g of thiourea aqueous solution into 3g of chitosan, stirring for 60min at 0 ℃, and centrifuging and defoaming to obtain a transparent chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into a methanol water solution with the water content of 70 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 290m by nitrogen adsorption2/g。
Example 32
Chitin is added at a concentration of 10.0 mol/kg-1Heating the mixture in sodium hydroxide aqueous solution for 2 hours to carry out deacetylation reaction, and obtaining the chitosan with deacetylation degree of about 70%. The concentration of 0.3 mol/kg is prepared in advance-11.2 mol/kg of lithium bicarbonate-195g of thiourea aqueous solution, 5g of chitosan is added, the mixture is stirred for 60min at the temperature of 0 ℃, and a transparent chitosan solution is obtained after centrifugal deaeration. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 4%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into a methanol water solution with the water content of 50 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 320m by nitrogen adsorption2/g。
Example 33
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 0.3 mol/kg is prepared in advance-1Sodium bicarbonate-1.2 mol/kg-195g of thiourea aqueous solution, 5g of chitosan is added,stirring at 10 deg.C for 60min, centrifuging, and defoaming to obtain transparent chitosan solution. Mixing chitosan stock solution with 2 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%), stirring at room temperature at 900rpm for 2 hr to form microsphere. And pouring the obtained microspheres into a methanol water solution with the water content of 30 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 250m by nitrogen adsorption2/g。
Example 34
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 0.3 mol/kg is prepared in advance-1Potassium bicarbonate-1.2 mol/kg-195g of thiourea aqueous solution, 5g of chitosan is added, the mixture is stirred for 120min at the temperature of 20 ℃, and a transparent chitosan solution is obtained after centrifugal deaeration. Mixing chitosan stock solution and 2 times volume ratio of oil phase (olive oil and span 80, span 80 concentration is 0.5%), stirring at room temperature at 900rpm for 2h to form microspheres. And pouring the obtained microspheres into a methanol water solution with the water content of 10 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 250m by nitrogen adsorption2/g。
Example 35
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 0.3 mol/kg is prepared in advance-1Ammonium bicarbonate-1.2 mol/kg-195g of thiourea aqueous solution, 5g of chitosan is added, the mixture is stirred for 120min at 10 ℃, and a transparent chitosan solution is obtained after centrifugal deaeration. Chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 ratio)5%) and then stirred at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into a potassium chloride aqueous solution with the mass fraction of 10 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 320m by nitrogen adsorption2/g。
Example 36
Chitin is added at a concentration of 12.5 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 35min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 0.3 mol/kg is prepared in advance-1Magnesium bicarbonate-1.2 mol/kg-195g of thiourea aqueous solution, 5g of chitosan is added, the mixture is stirred for 120min at 10 ℃, and a transparent chitosan solution is obtained after centrifugal deaeration. Mixing the chitosan stock solution and 1 volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into a potassium acetate aqueous solution with the mass fraction of 20 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 250m by nitrogen adsorption2/g。
Example 37
Chitin is added at a concentration of 12.5 mol/kg-1Heating the mixture in sodium hydroxide aqueous solution for 2 hours to carry out deacetylation reaction, and obtaining the chitosan with deacetylation degree of about 70%. The concentration of 0.8 mol/kg is prepared in advance-10.4 mol/kg of lithium bicarbonate-1Adding 94g of thiourea aqueous solution into 6g of chitosan, stirring for 30min at 0 ℃, and centrifuging and defoaming to obtain a transparent chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, the concentration of span 80 is 0.5%), stirring at room temperature at 900rpm for 2h to form microspheres. Pouring the obtained microspheres into 10 wt% of sodium citrate aqueous solution for re-treatmentAnd (3) raw materials are centrifuged, precipitates are taken and washed by petroleum ether, acetone, ethanol, acetone and water in sequence, and then the precipitates are frozen and dried to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 10 microns. The BET specific surface area is 400m by nitrogen adsorption2/g。
Example 38
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 0.8 mol/kg is prepared in advance-1Sodium bicarbonate-0.4 mol/kg-1Adding 94g of thiourea aqueous solution into 6g of chitosan, stirring for 100min at 10 ℃, and centrifuging and defoaming to obtain a transparent chitosan solution. Mixing the chitosan stock solution and 1 volume ratio of oil phase (olive oil and span 80, span 80 is 4%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into 10 wt% potassium chloride-30 wt% ethanol water solution for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 250m by nitrogen adsorption2/g。
Example 39
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 0.8 mol/kg is prepared in advance-1Potassium bicarbonate-0.4 mol/kg-1Adding 94g of thiourea aqueous solution into 6g of chitosan, stirring for 180min at 20 ℃, and centrifuging and defoaming to obtain a transparent chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 4%) and stirring at 900rpm for 2h at room temperature to form microspheres. Pouring the obtained microspheres into 10 wt% magnesium chloride-40 wt% ethanol aqueous solution for regeneration, centrifuging, taking precipitate, sequentially washing with petroleum ether, acetone, ethanol, acetone and water, and freeze-drying to obtain chitosanSugar microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 320m by nitrogen adsorption2/g。
Example 40
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 0.8 mol/kg is prepared in advance-1Ammonium bicarbonate-0.4 mol/kg-1Adding 94g of thiourea aqueous solution into 6g of chitosan, stirring for 100min at 10 ℃, and centrifuging and defoaming to obtain a transparent chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into 10 wt% of aluminum chloride-40 wt% of ethanol aqueous solution for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 250m by nitrogen adsorption2/g。
EXAMPLE 41
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 0.8 mol/kg is prepared in advance-1Magnesium bicarbonate-0.4 mol/kg-1Adding 94g of thiourea aqueous solution into 6g of chitosan, stirring for 100min at 10 ℃, and centrifuging and defoaming to obtain a transparent chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into 10 wt% calcium chloride-40 wt% ethanol water solution for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. Observing the morphology of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres to obtain the chitosan microspheres with the average size of 30 microns. The BET specific surface area is 250m by nitrogen adsorption2/g。
Example 42
Chitin is added at a concentration of 10.0 mol/kg-1Heating the mixture in sodium hydroxide aqueous solution for 2 hours to carry out deacetylation reaction, and obtaining the chitosan with deacetylation degree of about 70%. The concentration of 1.2 mol/kg was prepared in advance-11 mol/kg of lithium bicarbonate-1And adding 97g of thiourea aqueous solution into 3g of chitosan, stirring for 60min at 0 ℃, and centrifuging and defoaming to obtain a transparent chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into 10 wt% of magnesium chloride-40 wt% of methanol aqueous solution for regeneration, centrifuging, taking precipitates, washing the precipitates with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 320m by nitrogen adsorption2/g。
Example 43
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 1.2 mol/kg was prepared in advance-1Sodium bicarbonate-1 mol/kg-1And adding 97g of thiourea aqueous solution into 3g of chitosan, stirring for 120min at 10 ℃, and centrifuging and defoaming to obtain a transparent chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into 5 wt% of aluminum chloride-40 wt% of methanol aqueous solution for regeneration, centrifuging, taking precipitates, washing the precipitates with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 10 microns. The BET specific surface area is 340m by nitrogen adsorption2/g。
Example 44
Adding chitin to the solution at a concentration of 11.5 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 1.2 mol/kg was prepared in advance-1Potassium bicarbonate-1 mol/kg-1And adding 97g of thiourea aqueous solution into 3g of chitosan, stirring for 120min at 20 ℃, and centrifuging and defoaming to obtain a transparent chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into an ethanol water solution with the water content of 70 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 250m by nitrogen adsorption2/g。
Example 45
Adding chitin to the solution at a concentration of 11.5 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 1.2 mol/kg was prepared in advance-1Ammonium bicarbonate-1 mol/kg-1And adding 97g of thiourea aqueous solution into 3g of chitosan, stirring for 60min at 20 ℃, and centrifuging and defoaming to obtain a transparent chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into an ethanol water solution with the water content of 50 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 320m by nitrogen adsorption2/g。
Example 46
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating in potassium hydroxide water solution for 40min to perform deacetylation reaction to obtain deacetylation degree of about 70%The chitosan of (4). The concentration of 1.2 mol/kg was prepared in advance-1Magnesium bicarbonate-1 mol/kg-1And adding 97g of thiourea aqueous solution into 3g of chitosan, stirring for 60min at 10 ℃, and centrifuging and defoaming to obtain a transparent chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into an ethanol water solution with the water content of 30 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 250m by nitrogen adsorption2/g。
Example 47
Chitin is added at a concentration of 12.5 mol/kg-1Heating the mixture in sodium hydroxide aqueous solution for 2 hours to carry out deacetylation reaction, and obtaining the chitosan with deacetylation degree of about 70%. The concentration of 1.5 mol/kg was prepared in advance-10.4 mol/kg of lithium bicarbonate-1And adding 98g of thiourea aqueous solution into 2g of chitosan, stirring for 60min at 0 ℃, dissolving the chitosan, and performing centrifugal deaeration to obtain a transparent chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into an ethanol water solution with the water content of 20 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 10 microns. The BET specific surface area is 350m by nitrogen adsorption2/g。
Example 48
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 90min to perform deacetylation reaction to obtain chitosan with a deacetylation degree of about 80%. The concentration of 1.5 mol/kg was prepared in advance-1Sodium bicarbonate-0.4 mol/kg-198g of thiourea solution, 2g of chitosan was added thereto at 10 ℃Stirring for 30min, and centrifuging and defoaming to obtain a transparent chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into an ethanol water solution with the water content of 10 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 320m by nitrogen adsorption2/g。
Example 49
Chitin is added at a concentration of 10.0 mol/kg-1Heating in potassium hydroxide water solution for 50min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 1.5 mol/kg was prepared in advance-1Potassium bicarbonate-0.4 mol/kg-1And adding 98g of thiourea aqueous solution into 2g of chitosan, stirring for 200min at 15 ℃, and centrifuging and defoaming to obtain a transparent chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 6%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into a methanol water solution with the water content of 70 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 320m by nitrogen adsorption2/g。
Example 50
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating in potassium hydroxide water solution for 50min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 1.5 mol/kg was prepared in advance-1Ammonium bicarbonate-0.4 mol/kg-1And adding 98g of thiourea aqueous solution into 2g of chitosan, stirring for 120min at 5 ℃, and centrifuging and defoaming to obtain a transparent chitosan solution. Mixing chitosan stock solution with 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%),the microspheres are formed after stirring for 2 hours at room temperature at the rotating speed of 900 rpm. And pouring the obtained microspheres into a methanol water solution with the water content of 50 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 260m by nitrogen adsorption2/g。
Example 51
Adding chitin to the solution at a concentration of 11.5 mol/kg-1Heating in potassium hydroxide water solution for 50min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 0.8 mol/kg is prepared in advance-1Ammonium bicarbonate-1 mol/kg-1Urea-0.4 mol/kg-1Thiourea solution 98g was added with 2g chitosan and stirred at 5 ℃ for 120 min. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into a methanol water solution with the water content of 30 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 310m by nitrogen adsorption2/g。
Example 52
2g of analytically pure chitosan was dissolved in 98g of a solution having a concentration of 0.1 mol/kg-1Acetic acid-0.3 mol/kg-1Adding sodium hydroxide with equal molar ratio into acidic aqueous solution of urea for neutralization, precipitating chitosan, and adding sodium bicarbonate to make final concentration of 0.3 mol/kg-1Sodium bicarbonate, stirring at 10 deg.C for 10min to obtain chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. Pouring the obtained microspheres into 10 wt% methanol water solution for regeneration, centrifuging, collecting precipitate, sequentially washing with petroleum ether, acetone, ethanol, acetone and waterAnd (5) washing, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 280m by nitrogen adsorption2/g。
Example 53
3g of analytically pure chitosan was dissolved in 97g of a solution having a concentration of 0.5 mol/kg-1Acetic acid-1.0 mol.kg-1Adding sodium carbonate into acidic aqueous solution of urea at equal molar ratio for neutralization, precipitating chitosan, and adding sodium bicarbonate to make final concentration 1.2 mol/kg-1Sodium bicarbonate, stirring at 15 deg.C for 30min to obtain chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into an ethanol water solution with the water content of 70 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 270m by nitrogen adsorption2/g。
Example 54
3g of analytically pure chitosan was dissolved in 97g of 1.0 mol/kg-1Acetic acid-4.0 mol/kg-1Adding potassium bicarbonate with equal molar ratio into acidic aqueous solution of urea for neutralization, precipitating chitosan, and adding sodium bicarbonate to make its final concentration be 1.0 mol/kg-1Sodium bicarbonate, stirring at 10 deg.C for 10min to obtain chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into an ethanol water solution with the water content of 50 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 10 microns. The BET specific surface area is 350m by nitrogen adsorption2/g。
Example 55
2g of analytically pure chitosan was dissolved in 98g of a solution having a concentration of 0.1 mol/kg-1Hydrochloric acid-5.0 mol.kg-1Adding ammonium carbonate into acidic aqueous solution of urea at equal molar ratio for neutralization to precipitate chitosan, and adding potassium bicarbonate to make its final concentration be 0.3 mol/kg-1And (3) stirring potassium bicarbonate at 5 ℃ for 10min to obtain a chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into an ethanol water solution with the water content of 30 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 290m by nitrogen adsorption2/g。
Example 56
3g of analytically pure chitosan was dissolved in 97g of a solution having a concentration of 0.5 mol/kg-1Hydrochloric acid-1.0 mol.kg-1Adding magnesium bicarbonate with equal molar ratio into acidic aqueous solution of urea for neutralization, precipitating chitosan, and adding potassium bicarbonate to make its final concentration be 1.2 mol/kg-1Potassium bicarbonate, stirring at 0 deg.C for 10min to obtain chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into an ethanol water solution with the water content of 10 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 310m by nitrogen adsorption2/g。
Example 57
2g of analytically pure chitosan was dissolved in 98g of 1.0 mol/kg-1Hydrochloric acid-4.0 mol.kg-1UreaAdding ammonia water with equal molar ratio into the acidic aqueous solution to neutralize, precipitating chitosan, and adding magnesium bicarbonate to make the final concentration of 0.2 mol/kg-1Stirring magnesium bicarbonate at 10 deg.C for 10min to obtain chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into a potassium nitrate aqueous solution with the mass fraction of 30 wt% for regeneration, centrifuging, taking precipitates, washing the precipitates with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 320m by nitrogen adsorption2/g。
Example 58
2g of analytically pure chitosan was dissolved in 98g of a solution having a concentration of 0.1 mol/kg-1Citric acid-0.3 mol/kg-1Adding sodium hydroxide with equal molar ratio into acidic aqueous solution of urea for neutralization to precipitate chitosan, and adding potassium bicarbonate to make its final concentration be 1.5 mol/kg-1And (3) stirring potassium bicarbonate at 5 ℃ for 10min to obtain a chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into an ethanol water solution with the water content of 15 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 290m by nitrogen adsorption2/g。
Example 59
3g of analytically pure chitosan was dissolved in 97g of a solution having a concentration of 0.5 mol/kg-1Citric acid-1.0 mol/kg-1Adding potassium hydroxide with equal molar ratio into acidic aqueous solution of urea for neutralization to precipitate chitosan, and adding ammonium bicarbonate to make its final concentration be 1.2 mol/kg-1Stirring ammonium bicarbonate at 0 deg.C for 10min to obtainTo a chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into a potassium bromide aqueous solution with the mass fraction of 15 wt% for regeneration, centrifuging, taking precipitates, washing the precipitates with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 320m by nitrogen adsorption2/g。
Example 60
3g of analytically pure chitosan was dissolved in 98g of 1.0 mol/kg-1Citric acid-4.0 mol/kg-1Adding sodium hydroxide with equal molar ratio into acidic aqueous solution of urea for neutralization to precipitate chitosan, and adding magnesium bicarbonate to make its final concentration be 0.2 mol/kg-1Stirring magnesium bicarbonate at 10 deg.C for 10min to obtain chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into an ethanol water solution with the water content of 20 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 10 microns. The BET specific surface area is 340m by nitrogen adsorption2/g。
Example 61
Chitin is added at a concentration of 10.0 mol/kg-1Heating in potassium hydroxide water solution for 50min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 0.6 mol/kg is prepared in advance-1Sodium carbonate-2 mol/kg-1Adding 98g of urea aqueous solution, adding 2g of chitosan, introducing carbon dioxide to adjust the pH value of the solution to 10.0, stirring for 30min at 5 ℃, and performing centrifugal deaeration to obtain a transparent chitosan solution. Mixing chitosan stock solution with 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%), at room temperature,the microspheres are formed after stirring for 2 hours at the rotating speed of 900 rpm. And pouring the obtained microspheres into 10 wt% sodium chloride-10 wt% methanol aqueous solution for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 280m by nitrogen adsorption2/g。
Example 62
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating in potassium hydroxide water solution for 50min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 0.15 mol/kg is prepared in advance-1Ammonium carbonate-4 mol/kg-1Adding 98g of urea aqueous solution, adding 2g of chitosan, introducing carbon dioxide to adjust the pH value of the solution to 9.1, stirring for 60min at 5 ℃, and performing centrifugal deaeration to obtain a transparent chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 10%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into an ethanol water solution with the water content of 70 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 10 microns. The BET specific surface area is 340m by nitrogen adsorption2/g。
Example 63
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating in potassium hydroxide water solution for 50min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 0.3 mol/kg is prepared in advance-1Lithium hydroxide-5 mol/kg-1Adding 98g of urea aqueous solution, adding 2g of chitosan, introducing carbon dioxide to adjust the pH value of the solution to 7.0, stirring for 60min at 5 ℃, and performing centrifugal deaeration to obtain a transparent chitosan solution. Mixing chitosan stock solution with 2 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%), stirring at room temperature at 900rpm for 2 hr to form microsphere. Pouring the obtained microspheres intoRegenerating 5 wt% potassium acetate-25 wt% ethanol water solution, centrifuging, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microsphere. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 290m by nitrogen adsorption2/g。
Example 64
Adding chitin to the solution at a concentration of 11.5 mol/kg-1Heating in potassium hydroxide water solution for 50min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 0.8 mol/kg is prepared in advance-11 mol/kg of ammonia water-1Adding 98g of urea aqueous solution, adding 2g of chitosan, introducing carbon dioxide to adjust the pH value of the solution to 9.2, stirring for 60min at 5 ℃, and performing centrifugal deaeration to obtain a transparent chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into 10 wt% sodium chloride-20 wt% ethanol water solution for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 320m by nitrogen adsorption2/g。
Example 65
Chitin is added at a concentration of 11 mol/kg-1Heating in potassium hydroxide water solution for 50min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 0.2 mol/kg is prepared in advance-10.3 mol/kg of sodium hydroxide-1Adding 98g of urea aqueous solution, adding 2g of chitosan, introducing carbon dioxide to adjust the pH value of the solution to 8.7, stirring for 60min at 5 ℃, and performing centrifugal deaeration to obtain a transparent chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. Pouring the obtained microspheres into a calcium chloride aqueous solution with the mass fraction of 10 wt%Regenerating, centrifuging, taking the precipitate, washing with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microsphere. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 250m by nitrogen adsorption2/g。
Example 66
Chitin is added at a concentration of 11 mol/kg-1Heating in potassium hydroxide water solution for 50min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 1.5 mol/kg was prepared in advance-15 mol/kg of potassium hydroxide-1Adding 98g of urea aqueous solution, adding 2g of chitosan, introducing carbon dioxide to adjust the pH value of the solution to 9.0, stirring for 60min at 5 ℃, and performing centrifugal deaeration to obtain a transparent chitosan solution. Mixing the chitosan stock solution with 15 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%), stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into a potassium sulfate aqueous solution with the mass fraction of 5 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 320m by nitrogen adsorption2/g。
Example 67
Chitin is added at a concentration of 10 mol/kg-1Heating in potassium hydroxide water solution for 50min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 0.75 mol/kg was prepared in advance-1Potassium carbonate-0.3 mol/kg-1And adding 98g of thiourea aqueous solution, adding 2g of chitosan, introducing carbon dioxide to adjust the pH value of the solution to 9.0, stirring for 12 hours at 35 ℃, and performing centrifugal deaeration to obtain a transparent chitosan solution. Mixing the chitosan stock solution with 50 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%), stirring at 900rpm for 2h at room temperature to form microspheres. Pouring the obtained microspheres into 10 wt% sodium acetate aqueous solution for regeneration, centrifuging, and sequentially mixing the precipitate with petroleum ether, acetone, ethanol,And washing with acetone and water, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 285m by nitrogen adsorption2/g。
Example 68
Chitin is added at a concentration of 12.5 mol/kg-1Heating in potassium hydroxide water solution for 50min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 0.1 mol/kg is prepared in advance-1Sodium carbonate-1.2 mol/kg-1Adding 98g of thiourea aqueous solution, adding 2g of chitosan, introducing carbon dioxide to adjust the pH value of the solution to 9.0, stirring for 60min at 5 ℃, and centrifuging and defoaming to obtain a transparent chitosan solution. Mixing the chitosan stock solution with 100 times volume ratio of oil phase (olive oil and span 80, span 80 is 4%) and stirring at 300rpm for 2h at room temperature to form microspheres. And (3) pouring the obtained microspheres into methanol for regeneration, centrifuging, taking precipitates, washing the precipitates with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres to obtain the average size of 200 microns. The BET specific surface area is 320m by nitrogen adsorption2/g。
Example 69
The concentration of 10 mol/kg is prepared in advance-1Adding 4g chitin into the sodium hydroxide aqueous solution, heating the mixture for 90min to perform deacetylation reaction, wherein the deacetylation degree is about 75%, cooling the mixture to room temperature, filtering, squeezing to remove excessive sodium hydroxide aqueous solution, adding water and urea, and adjusting the concentration of the sodium hydroxide solution to 0.2 mol/kg-1The concentration of urea is 2mol kg-1And introducing carbon dioxide into the alkali liquor to adjust the pH value of the solution to 10.0, stirring the solution for 60min at the temperature of 10 ℃, and centrifuging and defoaming the solution to obtain a transparent chitosan solution. Mixing the chitosan stock solution with 10 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%), stirring at 900rpm for 2h at room temperature to form microspheres. Pouring the obtained microspheres into 10 wt% methanol water solution for regeneration, centrifuging, and collecting precipitateWashing with petroleum ether, acetone, ethanol, acetone and water, and freeze drying to obtain the chitosan microsphere. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 360m by nitrogen adsorption2/g。
Example 70
The concentration of 12.5 mol/kg was prepared in advance-1Adding 4g chitin into the sodium hydroxide aqueous solution, heating the mixture for 90min to perform deacetylation reaction, wherein the deacetylation degree is about 80%, cooling the mixture to room temperature, filtering, squeezing to remove excessive sodium hydroxide aqueous solution, adding water and urea, and adjusting the concentration of the sodium hydroxide solution to 0.3 mol/kg-1The concentration of urea is 2mol kg-1And introducing carbon dioxide into the alkali liquor to adjust the pH of the solution to 9.0, stirring at 10 ℃ for 60min, and centrifuging and defoaming to obtain a transparent chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into a methanol water solution with the water content of 30 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the morphology of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 70 microns. The BET specific surface area is 290m by nitrogen adsorption2/g。
Example 71
The concentration of 10 mol/kg is prepared in advance-1Adding 4g chitin into the potassium hydroxide aqueous solution, heating the mixture for 90min to perform deacetylation reaction, wherein the deacetylation degree is about 75%, cooling the mixture to room temperature, filtering, squeezing to remove excessive potassium hydroxide aqueous solution, adding water and urea, and adjusting the concentration of the potassium hydroxide solution to 0.8 mol/kg-1The concentration of urea is 5mol kg-1And introducing carbon dioxide into the alkali liquor to adjust the pH value of the solution to 7.0, stirring the solution for 60min at the temperature of 10 ℃, and centrifuging and defoaming the solution to obtain a transparent chitosan solution. Chitosan stock solution and 4 times volume ratio of oil phase (olive)Oil and tween 80, the concentration of span 80 is 10%), and the microspheres are formed after stirring at the rotating speed of 900rpm for 2 hours at room temperature. And pouring the obtained microspheres into a methanol water solution with the water content of 50 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres to obtain the average size of 100 microns. The BET specific surface area is 320m by nitrogen adsorption2/g。
Example 72
The concentration of 12.5 mol/kg was prepared in advance-1Adding 4g chitin into the potassium hydroxide aqueous solution, heating the mixture for 90min to perform deacetylation reaction, wherein the deacetylation degree is about 80%, cooling the mixture to room temperature, filtering, squeezing to remove excessive potassium hydroxide aqueous solution, adding water and urea, and adjusting the concentration of the potassium hydroxide solution to 0.8 mol/kg-1The concentration of urea is 4mol kg-1And introducing carbon dioxide into the alkali liquor to adjust the pH value of the solution to 9, stirring the solution for 60min at the temperature of 10 ℃, and centrifuging and defoaming the solution to obtain a transparent chitosan solution. Mixing the chitosan stock solution and 5 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%) and stirring at 900rpm for 2h at room temperature to form microspheres. And pouring the obtained microspheres into a methanol water solution with the water content of 70 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the morphology of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 70 microns. The BET specific surface area is 260m by nitrogen adsorption2/g。
Example 73
The concentration of 12.5 mol/kg was prepared in advance-1Adding 4g chitin into the potassium hydroxide aqueous solution, heating the mixture for 90min to perform deacetylation reaction, wherein the deacetylation degree is about 80%, cooling the mixture to room temperature, filtering, squeezing to remove excessive potassium hydroxide aqueous solution, adding water and urea, and adjusting the concentration of the potassium hydroxide solution to 1.5 mol/kg-1Concentration of ureaIs 4 mol/kg-1And introducing carbon dioxide into the alkali liquor to adjust the pH value of the solution to 9, stirring the solution for 60min at the temperature of 10 ℃, and centrifuging and defoaming the solution to obtain a transparent chitosan solution. Mixing the chitosan stock solution with 100 times volume ratio of oil phase (olive oil and span 80, span 80 is 5%), stirring at 900rpm for 2h at room temperature to form microspheres. And (3) pouring the obtained microspheres into ethanol for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres to obtain the average size of 100 microns. The BET specific surface area is 250m by nitrogen adsorption2/g。
Example 74
The concentration of 12.5 mol/kg was prepared in advance-1Adding 4g chitin into the potassium hydroxide aqueous solution, heating the mixture for 90min to perform deacetylation reaction, wherein the deacetylation degree is about 80%, cooling the mixture to room temperature, filtering, squeezing to remove excessive potassium hydroxide aqueous solution, adding water and urea, and adjusting the concentration of the potassium hydroxide solution to 1.2 mol/kg-1The concentration of urea is 4mol kg-1And introducing carbon dioxide into the alkali liquor to adjust the pH of the solution to 9.0, stirring at 10 ℃ for 60min, and centrifuging and defoaming to obtain a transparent chitosan solution. And adding 1% by mass of sodium alginate into the chitosan solution, stirring for dissolving, and performing centrifugal deaeration to obtain the chitosan/sodium alginate solution. Mixing chitosan/sodium alginate solution and 10 times volume ratio of oil phase (olive oil and span 80, span 80 is 10%), stirring at room temperature at 900rpm for 2h to form microsphere. And pouring the obtained microspheres into an ethanol water solution with the water content of 10 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan/sodium alginate microspheres. And observing the appearance of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 30 microns. The BET specific surface area is 250m by nitrogen adsorption2/g。
Example 75
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 1.2 mol/kg was prepared in advance-1Potassium bicarbonate-4 mol/kg-1Adding 0.5g of graphene oxide into 97g of urea aqueous solution, performing ultrasonic dispersion, adding 2.5g of chitosan, stirring for 120min at 20 ℃, and performing centrifugal deaeration to obtain a transparent chitosan/graphene oxide solution. Mixing the chitosan/graphene oxide stock solution with an oil phase (olive oil and tween 80, the concentration of the tween 80 is 0.5%) in a volume ratio of 2.5 times, and stirring at the rotating speed of 900rpm for 2 hours at room temperature to form microspheres. And pouring the obtained microspheres into an ethanol water solution with the water content of 30 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan/graphene oxide microspheres. And observing the morphology of the chitosan microspheres by using a scanning electron microscope, and counting the diameters of the microspheres, wherein the average size of the microspheres is 40 micrometers. The BET specific surface area is 350m by nitrogen adsorption2(ii) in terms of/g. Adsorption experiments show that the chitosan/graphene oxide microspheres have a good effect on tetracycline, and 400mg of tetracycline can be adsorbed by every 1g of chitosan/graphene oxide microspheres.
Example 76
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 1.2 mol/kg was prepared in advance-1Potassium bicarbonate-4 mol/kg-1Adding 0.5g of graphene oxide into 97g of urea aqueous solution, performing ultrasonic dispersion, adding 2.5g of chitosan, stirring for 120min at 20 ℃, and performing centrifugal deaeration to obtain a transparent chitosan/graphene oxide solution. Mixing the chitosan/graphene oxide stock solution with an oil phase (olive oil and tween 80, the concentration of the tween 80 is 0.5%) in a volume ratio of 2.5 times, and stirring at the rotating speed of 900rpm for 2 hours at room temperature to form microspheres. And pouring the obtained microspheres into an ethanol water solution with the water content of 50 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan/graphene oxide microspheres. Heating the obtained chitosan/graphene oxide microspheres to 1000 ℃ from room temperature at a speed of 10 ℃/min, and taking nitrogen as protectionAnd (5) gas is generated to obtain the nitrogen element doped carbon aerogel microspheres. The specific surface area of the carbon aerogel obtained by the nitrogen adsorption-desorption experiment is 1089m2/g。
Example 77
Adding chitin to the solution at a concentration of 11.0 mol/kg-1Heating the mixture in a potassium hydroxide aqueous solution for 40min to perform deacetylation reaction to obtain chitosan with deacetylation degree of about 70%. The concentration of 1.2 mol/kg was prepared in advance-1Potassium bicarbonate-4 mol/kg-1Adding 3g of chitosan into 97g of urea aqueous solution, stirring for 120min at 20 ℃, and performing centrifugal deaeration to obtain a transparent chitosan solution. Mixing chitosan solution and 2 times volume ratio of oil phase (olive oil and span 80, span 80 concentration is 0.5%), stirring at room temperature at 900rpm for 2h to form microspheres. And pouring the obtained microspheres into an ethanol water solution with the water content of 70 wt% for regeneration, centrifuging, taking the precipitate, washing the precipitate with petroleum ether, acetone, ethanol, acetone and water in sequence, and freeze-drying to obtain the chitosan microspheres. And heating the obtained chitosan microspheres to 1000 ℃ from room temperature at a speed of 10 ℃/min, and taking nitrogen as protective gas to obtain the nitrogen-doped carbon aerogel microspheres. The specific surface area of the carbon aerogel obtained by the nitrogen adsorption-desorption experiment is 1179m2/g。

Claims (17)

1. A preparation method of a chitosan microsphere material is characterized by comprising the following steps:
(1) preparing a weakly alkaline aqueous solution, wherein the weakly alkaline aqueous solution consists of bicarbonate, a stabilizer and water; wherein the final concentration of bicarbonate is: 0.2 to 1.5 mol/kg-1The final concentration of the stabilizer is 0.3-5.0 mol/kg-1Urea or 0.3-1.2 mol/kg-1Thiourea or a mixture of the two, and the balance water;
(2) preparing a chitosan weakly alkaline aqueous solution: adding chitosan into the alkalescent aqueous solution obtained in the step (1), continuously stirring for more than 30 minutes under the condition that the freezing point is 35 ℃, and defoaming to obtain a transparent chitosan solution;
(3) preparing a chitosan microsphere material: forming chitosan emulsion drops by the chitosan alkalescent aqueous solution and the oil phase obtained in the step (2) in a certain mode, and solidifying the emulsion drops to form chitosan microspheres; the oil phase consists of an oily substance which is liquid at normal temperature and is immiscible with water and an oil-soluble emulsifier; the chitosan emulsion droplet forming mode comprises the utilization of a conventional stirring device, a microfluidic device and a membrane emulsifier;
the bicarbonate is a single bicarbonate aqueous solution or a mixture of multiple bicarbonates aqueous solutions.
2. The method for preparing chitosan microsphere material according to claim 1, wherein the preferable concentration of bicarbonate in the weakly alkaline aqueous solution prepared in step (1) is 0.3-1.2 mol-kg-1The stabilizer is 1.0-4.0 mol/kg-1Urea or 0.4-1.0 mol/kg-1Thiourea and the balance water.
3. A preparation method of a chitosan microsphere material is characterized by comprising the following steps:
(1) dissolving chitosan in a stabilizer at a concentration of 0.1-1.0 mol/kg-1Adding a proper amount of alkali to the inorganic or organic acid aqueous solution to adjust the pH of the solution to be neutral, and separating out chitosan; the stabilizer is 0.3-5.0 mol/kg of final concentration-1Urea or 0.3-1.2 mol/kg-1Thiourea or a mixture of the two; the alkali for adjusting the pH of the solution is any one of alkali hydroxide, alkali metal carbonate, alkaline earth metal carbonate, alkali metal bicarbonate, alkaline earth metal bicarbonate, ammonia water, ammonium carbonate and ammonium bicarbonate or a mixture of the alkali hydroxide, the alkali metal carbonate, the alkaline earth metal bicarbonate and the ammonia water; the inorganic or organic acid is preferably acetic acid, hydrochloric acid, citric acid, etc.;
(2) adding bicarbonate into the mixture of chitosan and water in the step (1), continuously stirring for more than 10 minutes under the condition of the freezing point to 35 ℃, dissolving the chitosan, and defoaming to obtain a transparent chitosan solution; the final concentration of the bicarbonate is 0.2-1.5 mol/kg-1；
(3) Preparing a chitosan microsphere material: forming chitosan emulsion drops by the chitosan alkalescent aqueous solution and the oil phase obtained in the step (2) in a certain mode, and solidifying the emulsion drops to form chitosan microspheres; the oil phase consists of an oily substance which is liquid at normal temperature and is immiscible with water and an oil-soluble emulsifier; the chitosan emulsion droplet forming mode comprises the utilization of a conventional stirring device, a microfluidic device and a membrane emulsifier;
the bicarbonate is a single bicarbonate aqueous solution or a mixture of multiple bicarbonates aqueous solutions.
4. The method for preparing chitosan microsphere material according to claim 3, wherein the final concentration of the stabilizer added in step (1) is preferably in the range of 1.0-4.0 mol-kg-1Urea or 0.4-1.0 mol/kg-1Thiourea; the final concentration range of the bicarbonate in the step (2) is preferably 0.3-1.2 mol/kg-1。
5. A preparation method of a chitosan microsphere material is characterized by comprising the following steps:
(1) preparing an alkaline aqueous solution, wherein the alkaline aqueous solution consists of alkaline hydroxide or carbonate, a stabilizing agent and water; wherein the final concentration of the alkali hydroxide is 0.2 to 1.5 mol/kg-1The final concentration of carbonate is 0.10 to 0.75 mol/kg-1The final concentration of the stabilizer is 0.3-5.0 mol/kg-1Urea or 0.3-1.2 mol/kg-1Thiourea or a mixture of the thiourea and the water;
(2) adding chitosan into the alkaline aqueous solution obtained in the step (1), introducing carbon dioxide, continuously stirring for more than 30 minutes under the condition that the freezing point is 35 ℃, dissolving the chitosan when the pH value of the solution is about 7-10, and defoaming to obtain a transparent chitosan solution;
(3) preparing a chitosan microsphere material: forming chitosan emulsion drops by the chitosan alkalescent aqueous solution and the oil phase obtained in the step (2) in a certain mode, and solidifying the emulsion drops to form chitosan microspheres; the oil phase consists of an oily substance which is liquid at normal temperature and is immiscible with water and an oil-soluble emulsifier; the chitosan emulsion droplet forming mode comprises the utilization of a conventional stirring device, a microfluidic device and a membrane emulsifier;
the bicarbonate is a single bicarbonate aqueous solution or a mixture of multiple bicarbonates aqueous solutions; the alkaline hydroxide is metal hydroxide, ammonium hydroxide, quaternary ammonium base, preferably sodium hydroxide, potassium hydroxide, ammonium hydroxide or a mixture thereof; the carbonate is preferably sodium carbonate, potassium carbonate, ammonium carbonate, or a mixture thereof.
6. The preparation method of chitosan microsphere material according to claim 5, wherein the final concentration of alkali hydroxide in the alkaline aqueous solution prepared in step (1) is preferably 0.3-1.2 mol-kg-1The final concentration of carbonate is preferably 0.15 to 0.6 mol/kg-1The stabilizer is preferably at a final concentration of 1.0 to 4.0 mol/kg-1Urea or 0.4-1.0 mol/kg-1Thiourea and the balance water.
7. A preparation method of a chitosan microsphere material is characterized by comprising the following steps:
1) chitin and the mass molar concentration of 8.0-12.5 mol/kg-1Mixing sodium hydroxide aqueous solution or potassium hydroxide aqueous solution, heating to perform deacetylation reaction to generate chitosan;
(2) adjusting the final concentration of sodium hydroxide or potassium hydroxide in the mixture obtained in (1) to 0.2-1.5 mol/kg-1Reducing the temperature of the mixture to between the freezing point and 35 ℃, adding a stabilizer, introducing carbon dioxide at room temperature, converting sodium hydroxide or potassium hydroxide into bicarbonate when the pH value of the solution is about 7-10, stirring for more than 30 minutes to dissolve chitosan, and defoaming to obtain a transparent chitosan solution; the stabilizer is 0.3-5.0 mol/kg of final concentration-1Urea or 0.3-1.2 mol/kg-1One or a mixture of two of thiourea; preferably, the final concentration of the stabilizer is 1.0-4.0 mol/kg-1Urea or 0.4-1.0 mol/kg-1One or a mixture of two of thiourea; preferably, the final concentration of the bicarbonate is 0.3-1.2 mol-kg-1；
(3) Preparing a chitosan microsphere material: forming chitosan emulsion drops by the chitosan alkalescent aqueous solution and the oil phase obtained in the step (2) in a certain mode, and solidifying the emulsion drops to form chitosan microspheres; the oil phase consists of an oily substance which is liquid at normal temperature and is immiscible with water and an oil-soluble emulsifier; the chitosan emulsion droplet forming mode comprises the utilization of a conventional stirring device, a microfluidic device and a membrane emulsifier;
the bicarbonate is a single bicarbonate aqueous solution or a mixture of multiple bicarbonates aqueous solutions.
8. The method for preparing the chitosan microsphere material of claim 7, wherein: the method for adjusting the concentration of sodium hydroxide or potassium hydroxide in the mixture in the step (2) comprises the following steps: filtering and squeezing the mixture obtained in the step (1) to remove excessive sodium hydroxide or potassium hydroxide aqueous solution, and adding a proper amount of water to ensure that the final concentration of the sodium hydroxide or the potassium hydroxide in the mixture is 0.2-1.5 mol/kg-1。
9. The method for preparing the chitosan microsphere material according to claims 1 to 8, wherein the method comprises the following steps: the oily substance in the step (3) is liquid paraffin, petroleum ether, olive oil, cottonseed oil, soybean oil, sunflower seed oil, other alkane hydrocarbons and the like; as the oily emulsifier, there may be used those which are soluble in the oily substance to be used, sorbitan sesquioleate (Arlace183), polymers of glyceryl ether (e.g., PO-500, PO-310), polyoxyethylene hydrogenated castor oil, sorbitan trioleate (span 85), sorbitan monooleate (span 80), sorbitan tristearate (span 65), tween 80, lipophilic-hydrophilic block copolymer, etc.; the concentration of the emulsifier in the oil phase is 0.5-10%.
10. The preparation method of the chitosan microsphere material of any one of claims 1 to 8, wherein the volume ratio of the chitosan solution to the oil phase is 1:1 to 1:1000, preferably 1:2 to 1: 100.
11. The method for preparing chitosan microsphere material of any one of claims 1 to 8, wherein the bicarbonate comprises one or more of alkali metal bicarbonate, alkaline earth metal bicarbonate, and ammonium bicarbonate, preferably sodium bicarbonate, potassium bicarbonate, ammonium bicarbonate, and magnesium bicarbonate.
12. The method for preparing the chitosan microsphere material according to any one of claims 1 to 8, wherein the manner of forming the chitosan microsphere after solidifying the emulsion droplets is by using a chemical crosslinking agent, including aldehyde crosslinking agents, glycidyl ether crosslinking agents, epoxy compounds, iridoid, polyphenols, preferably glutaraldehyde, epichlorohydrin, genipin, procyanidine; the chemical cross-linking agent is a common cross-linking agent with the molar ratio of 0.1-10 equivalent to the chitosan monomer; or adopting coagulant which is one or more of mixed aqueous solution of amide, dimethyl sulfoxide, ethyl acetate, acetone, alcohol, salt and acid; the preferable salt concentration is 0-40 wt%, the acid concentration is 0-20 wt%, and the alcohol concentration is 0-100 wt%; the alcohol is preferably methanol or ethanol; the salt is preferably ammonium salt, sodium salt, potassium salt, magnesium salt, calcium salt, or aluminum salt.
13. The method for preparing the chitosan microsphere material of any one of claims 1 to 8, wherein the emulsion droplets are obtained by using a membrane emulsifier by pressing a chitosan aqueous solution (water phase) into an oil phase through a microporous membrane under pressure to obtain emulsion droplets with uniform size; the method for obtaining the emulsion drop by utilizing the microfluidic device is that a micro pump is used for conveying an oil phase and a water phase to two intersected channels in a microfluidic chip, and the oil phase is used as a continuous phase to separate the water phase to form a monodisperse emulsion drop; the method for obtaining the emulsion droplets by using the conventional stirring device is to mix the oil phase and the water phase, perform mechanical stirring, and disperse the water phase into the oil phase to form the emulsion droplets.
14. A chitosan microsphere material, which is characterized by being prepared by the preparation method of the chitosan material as claimed in any one of claims 1 to 13.
15. A preparation method of multifunctional chitosan microspheres is characterized in that functional organic or inorganic additives or different macromolecules are introduced for blending in the process of the preparation method of the chitosan microsphere material according to any one of claims 1 to 13, and the additives can be added through a chitosan stock solution or a coagulant; preferably, the functional organic or inorganic additive comprises one or more of a plasticizer, a reinforcing agent, a refractory material additive, a dye, an optical stabilizer, an antibacterial bacteriostatic agent, a conductive material and a surfactant; preferably, the functional organic or inorganic additive includes graphene and its derivatives, carbon nanotubes and their derivatives, metal or metal oxide nanoparticles, organic framework compounds or molybdenum disulfide, and the like, and the blended polymer includes polymer nanofibers, cellulose and its derivatives, animal proteins, vegetable proteins, collagen, alginate, conductive polymers, polyethylene glycol, polyvinyl alcohol, and the like.
16. A multifunctional chitosan microsphere material, characterized by being prepared by the method for preparing the multifunctional chitosan microsphere of claim 15.
17. A method for preparing nitrogen-doped carbon aerogel microspheres, which is characterized in that the chitosan microspheres of claim 14 or the multifunctional chitosan microspheres of claim 16 are subjected to heat treatment at a temperature of more than 150 ℃ under the protection of inert gas atmosphere to obtain the carbon aerogel microspheres.
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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112106975A (en) * 2020-09-30 2020-12-22 郑州轻工业大学 Chitin tannin composite colloidal particle emulsifier and preparation method and application thereof
CN113336977A (en) * 2021-05-19 2021-09-03 武汉大学 Chitosan nanofiber microsphere and preparation method thereof
CN114195135A (en) * 2021-12-31 2022-03-18 苏州知益微球科技有限公司 Preparation method and application of graphene microspheres
CN114213701A (en) * 2021-12-22 2022-03-22 安徽医科大学附属口腔医院 Polymer sponge microsphere and preparation method thereof
CN114984916A (en) * 2022-04-26 2022-09-02 贵州黔大生态环境与健康研究院有限公司 Chitosan nano-microsphere, preparation method and application thereof

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103756016A (en) * 2013-12-25 2014-04-30 武汉工程大学 Cellulose micro-sphere with uniform size as well as preparation method and application thereof
CN104722251A (en) * 2015-04-23 2015-06-24 福建师范大学 Preparation method of porous chitosan-based microspheres
CN106800662A (en) * 2017-01-23 2017-06-06 武汉大学 A kind of preparation method of chitosan gel rubber based material
CN108948377A (en) * 2017-05-18 2018-12-07 武汉大学 A kind of quick dissolution method of chitosan and its application

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103756016A (en) * 2013-12-25 2014-04-30 武汉工程大学 Cellulose micro-sphere with uniform size as well as preparation method and application thereof
CN104722251A (en) * 2015-04-23 2015-06-24 福建师范大学 Preparation method of porous chitosan-based microspheres
CN106800662A (en) * 2017-01-23 2017-06-06 武汉大学 A kind of preparation method of chitosan gel rubber based material
CN108948377A (en) * 2017-05-18 2018-12-07 武汉大学 A kind of quick dissolution method of chitosan and its application

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112106975A (en) * 2020-09-30 2020-12-22 郑州轻工业大学 Chitin tannin composite colloidal particle emulsifier and preparation method and application thereof
CN112106975B (en) * 2020-09-30 2023-03-31 郑州轻工业大学 Chitin tannin composite colloidal particle emulsifier and preparation method and application thereof
CN113336977A (en) * 2021-05-19 2021-09-03 武汉大学 Chitosan nanofiber microsphere and preparation method thereof
CN114213701A (en) * 2021-12-22 2022-03-22 安徽医科大学附属口腔医院 Polymer sponge microsphere and preparation method thereof
CN114195135A (en) * 2021-12-31 2022-03-18 苏州知益微球科技有限公司 Preparation method and application of graphene microspheres
CN114984916A (en) * 2022-04-26 2022-09-02 贵州黔大生态环境与健康研究院有限公司 Chitosan nano-microsphere, preparation method and application thereof
CN114984916B (en) * 2022-04-26 2024-03-08 贵州黔大生态环境与健康研究院有限公司 Chitosan nano microsphere, preparation method and application thereof

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